Allergies are caused by a dysfunction in the immune system, which reacts to innocuous proteins contained in pollen, mites, epithelia and certain foods by producing IgE-class antibodies.
Recent data indicate that above 10% of the population in Western countries suffers from this disease, the symptoms of which may deteriorate with time giving rise to e.g. asthma or a sensitization to other allergens thus making more difficult the choice of the appropriate therapy.
Specific hyposensitizing immunotherapy, unlike pharmacological therapy, is the only etiological treatment of allergic diseases capable of favourably changing the immunological parameters on which these diseases are based.
The hyposensitizing immunotherapy consists in the administration of increasing doses of standardized extracts (vaccines) obtained from the same substance which causes the disease (1). In this way, a sort of immunological tolerance to said substance is gradually induced in the patient with following disappearance of the allergic symptoms.
However, the risk of eliciting serious side effects (2), although remarkably reduced with the use of either slow-release vaccines or vaccines administered through routes alternative to injections, has in fact limited the application of specific hyposensitizing immunotherapy in the treatment of allergic diseases.
In recent years, most attention has been focused on the development of effective, safer vaccines. In particular, the development of vaccines consisting of mutagenized recombinant proteins, i.e. hypoallergenic variants capable of favourably influencing the natural progression of the disease without causing undesired side effects (3), has represented an important goal.
The pollen of plants taxonomically known as Fagales (birch, alder, hazel, oak, hornbeam) is one of the most important causes of allergic rhinitis and asthma in the temperate regions. The two major allergens of birch pollen, Bet v 1 (cDNA deposited at GenBank acc. No. X15877) and Bet v 2 (acc. No. M65179) are proteins with molecular weight of 17 and 14 kD, respectively (4,5). Nearly 95% of patients with allergy to birch pollen produce IgE antibodies against Bet v 1 and 60% of these patients show reactivity against Bet v 1 alone (6).
Bet v 1 is naturally present in over ten isoforms showing a sequence identity comprised between 84.4% and 99.4% (7). This allergen belongs to the family of ‘pathogenesis related proteins’, i.e. ubiquitous proteins produced by plants in response to environmental or pathology stress, the functions of which is supposed to be connected to steroid transport (8,9). The high sequence homology with the allergens of group 1 in pollen from other plants of the Fagales order explains why patients with IgE specific for Bet v 1 show allergic symptoms during the pollination season of different plants belonging to the same taxonomic order (10). The allergy to birch pollen is often accompanied by adverse reactions provoked by intake of fresh fruits (e.g. cherry, apple, pear) or vegetables (e.g. celery and carrot). The reason is that such foods contain proteins characterized by high sequence and structure homology to Bet v 1, which are recognized by specific IgEs raised by the birch major allergen (11). The immunotherapy with Bet v 1 allergen may be effective in the treatment of birch pollen allergy as well as pollinosis to other plants of the order Fagales and allergy to food containing allergens that cross-react with Bet v 1 (12).
A factor correlating to the beneficial effects of the hyposensitizing immunotherapy is the induction of IgG antibodies specific for the sensitizing allergen. Such (protecting) antibodies can inhibit the IgE binding to the antigen, specifically to Bet v 1, altering the tridimensional conformation of this molecule (13, 14). The development of vaccines consisting of recombinant proteins possessing less allergenicity and unaltered immunogenic properties would ameliorate the therapy of allergic diseases.